Fracchiolla D, Sawa-Makarska J, Zens B, de Ruiter A, Zaffagnini G, Brezovich A, Romanov J, Runggatscher K, Kraft C, Zagrovic B, Martens S

Selective autophagy is mediated by cargo receptors that link the cargo to the isolation membrane via interactions with Atg8 proteins. Atg8 proteins are localized to the membrane in an ubiquitin-like conjugation reaction, but how this conjugation is coupled to the presence of the cargo is unclear. Here we show that ...

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the S. cerevisiae Atg19, Atg34 and the human p62, Optineurin and NDP52 cargo receptors interact with the E3-like enzyme Atg12∼Atg5-Atg16, which stimulates Atg8 conjugation. The interaction of Atg19 with the Atg12∼Atg5-Atg16 complex is mediated by its Atg8-interacting motifs (AIMs). We identify the AIM-binding sites in the Atg5 subunit and mutation of these sites impairs selective autophagy. In a reconstituted system the recruitment of the E3 to the prApe1 cargo is sufficient to drive accumulation of conjugated Atg8 at the cargo. The interaction of the Atg12∼Atg5-Atg16 complex and Atg8 with Atg19 is mutually exclusive, which may confer directionality to the system.

Date: Nov. 23, 2016

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